Rahul S Bhansali, Keith W Pratz, Catherine Lai
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold with the optimization of intensive induction chemotherapy and allogeneic stem cell transplantation (alloHSCT), this effect has been largely mitigated in older and less fit patients as well as those with adverse-risk disease characteristics. However, the last 10 years has been marked by major advances in the molecular profiling of AML characterized by a deeper understanding of disease pathobiology and therapeutic vulnerabilities...
March 25, 2023: Journal of Hematology & Oncology
Zebin Yu, Jianhu Li, Xiang Wen, Yingli Han, Penglei Jiang, Meng Zhu, Minmin Wang, Xiangli Gao, Dan Shen, Ting Zhang, Shuqi Zhao, Yijing Zhu, Jixiang Tong, Shuchong Yuan, HongHu Zhu, He Huang, Pengxu Qian
Acute myeloid leukemia (AML) is a deadly hematological malignancy. Cellular morphology detection of bone marrow smears based on the French-American-British (FAB) classification system remains an essential criterion in the diagnosis of hematological malignancies. However, the diagnosis and discrimination of distinct FAB subtypes of AML obtained from bone marrow smear images are tedious and time-consuming. In addition, there is considerable variation within and among pathologists, particularly in rural areas, where pathologists may not have relevant expertise...
March 21, 2023: Journal of Hematology & Oncology
Binghao Zhao, Bo Wu, Nan Feng, Xiang Zhang, Xin Zhang, Yiping Wei, Wenxiong Zhang
The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated secretory phenotype (SASP)...
March 21, 2023: Journal of Hematology & Oncology
Shuling Chen, Jiaxin Li, Aoran Dong, Zelong Liu, Meiyan Zhu, Meng Jin, Guangyan Wei, Shuang Wu, Yan Wang, Yong Chen, Zhenwei Peng
Treatment options specifically for patients with locally advanced pancreatic adenocarcinoma (LAPC) are scare and chemotherapy alone delivers limited efficacy. Immunotherapy and radiotherapy are potential effective treatments for LAPC, and both of them may synergize with chemotherapy. Therefore, in this prospective cohort study, we compared the efficacy and safety of nab-paclitaxel plus gemcitabine combined with anti-programmed cell death (PD-1) immunotherapy and radiotherapy (hereafter, combination treatment) versus nab-paclitaxel plus gemcitabine (chemotherapy alone) in the treatment of LAPC...
March 20, 2023: Journal of Hematology & Oncology
Yishan Ye, Myriam Labopin, Jia Chen, Zafer Gulbas, Xi Zhang, Yener Koc, Didier Blaise, Fabio Ciceri, Emmanuelle Polge, Mohamed Houhou, Lin Li, Yi Luo, Depei Wu, He Huang, Mohamad Mohty, Norbert-Claude Gorin
There are situations where non-first-degree (NFD) related donors have to be considered as alternatives to first-degree (FD) related donors for haploidentical hematopoietic cell transplantation (HAPLO). However, the efficacy of these NFD related transplants remains uncertain. All consecutive adult patients (≥ 18 years) with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in CR who underwent a first HAPLO between 2010 and 2021 in the European Society for Blood and Marrow Transplantation (EBMT) registry were analyzed...
March 18, 2023: Journal of Hematology & Oncology
Sandra Genduso, Vera Freytag, Daniela Schetler, Lennart Kirchner, Alina Schiecke, Hanna Maar, Daniel Wicklein, Florian Gebauer, Katharina Bröker, Christine Stürken, Karin Milde-Langosch, Leticia Oliveira-Ferrer, Franz L Ricklefs, Florian Ewald, Gerrit Wolters-Eisfeld, Kristoffer Riecken, Ludmilla Unrau, Linda Krause, Hanibal Bohnenberger, Anne Offermann, Sven Perner, Susanne Sebens, Katrin Lamszus, Linda Diehl, Stefan Linder, Manfred Jücker, Udo Schumacher, Tobias Lange
BACKGROUND: The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin β4 (ITGB4) on tumor cells and E-/P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment. METHODS: We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic immune cell composition were determined by flow cytometry and immunohistochemistry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays...
March 17, 2023: Journal of Hematology & Oncology
Ziqi Zhang, Xue Li, Yang Wang, Yuquan Wei, Xiawei Wei
Inflammasomes are macromolecular platforms formed in response to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns, whose formation would cause maturation of interleukin-1 (IL-1) family members and gasdermin D (GSDMD), leading to IL-1 secretion and pyroptosis respectively. Several kinds of inflammasomes detecting different types of dangers have been found. The activation of inflammasomes is regulated at both transcription and posttranscription levels, which is crucial in protecting the host from infections and sterile insults...
March 17, 2023: Journal of Hematology & Oncology
Elias Jabbour, Nicholas J Short, Nitin Jain, Fadi G Haddad, Mary Alma Welch, Farhad Ravandi, Hagop Kantarjian
Progress in the research and therapy of adult acute lymphoblastic leukemia (ALL) is accelerating. This analysis summarizes the data derived from the clinical trials conducted at MD Anderson between 1985 and 2022 across ALL subtypes. In Philadelphia chromosome-positive ALL, the addition of BCR::ABL1 tyrosine kinase inhibitors (TKIs) to intensive chemotherapy since 2000, improved outcomes. More recently, a chemotherapy-free regimen with blinatumomab and ponatinib resulted in a complete molecular remission rate of 85% and an estimated 3-year survival rate of 90%, potentially reducing the role of, and need for allogeneic stem cell transplantation (SCT) in remission...
March 16, 2023: Journal of Hematology & Oncology
Jing Dong, Christopher Staffi Buradagunta, Tao Zhang, Stephen Spellman, Yung-Tsi Bolon, Amy E DeZern, Shahinaz M Gadalla, H Joachim Deeg, Aziz Nazha, Corey Cutler, Chao Cheng, Raul Urrutia, Paul Auer, Wael Saber
Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM)...
March 10, 2023: Journal of Hematology & Oncology
Chaoyu Wang, Yao Liu
Over one-third of B cell lymphomas are not effectively treated by R-CHOP chemotherapy. When lymphoma relapses or is refractory, the prognosis becomes very poor. Due to this fact, there is an urgent and clear requirement for a more effective, novel treatment option. Glofitamab is a CD20xCD3 T-cell-engaging, bispecific antibody capable of recruiting T cells to tumor cells. We have summarized several of the latest reports on glofitamab use in B cell lymphoma therapy from the 2022 ASH Annual Meeting (ASH2022).
March 10, 2023: Journal of Hematology & Oncology
Naval G Daver, Shahed Iqbal, Camille Renard, Rebecca J Chan, Ken Hasegawa, Hao Hu, Preston Tse, Jiajun Yan, Michael J Zoratti, Feng Xie, Giridharan Ramsingh
BACKGROUND: TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA). METHODS: We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML...
March 6, 2023: Journal of Hematology & Oncology
Qiusha Huang, Xiao-Hui Zhang, Delong Liu
Due to the concern of fratricide, clinical development of CAR T cells for the therapy of T cell malignancies lags behind that for B cell malignancies. Attempts are being made to revise T cell biomarkers so that the re-engineered CAR T cells can target T cell malignancies. CD3 and CD7 are the two pan-T cell surface biomarkers that have been either knocked out or knocked down through genome base- editing technology or by protein expression blockers so that the re-engineered T cells can target T cells without fratricide...
March 5, 2023: Journal of Hematology & Oncology
Katherine W DiNardo, Thomas W LeBlanc, Hui Chen
Developments in investigational agents and novel regimens in acute myeloid leukemia (AML) were reported in the 2022 American Society of Hematology (ASH) annual meeting. Encouraging efficacy data were presented from first-in-human studies of two investigational menin inhibitors, SNDX-5613 and KO-539, in relapsed and refractory (R/R) acute myeloid leukemia (AML) with KMT2A rearrangement or mutant NPM1, with overall response rates (ORR) of 53% (32/60) and 40% (8/20), respectively. The addition of the novel drug pivekimab sunirine, a first-in-class antibody-drug conjugate targeting CD123, to azacitidine and venetoclax in R/R AML resulted in an ORR of 45% (41/91), which rose to 53% in those who were venetoclax naïve...
March 3, 2023: Journal of Hematology & Oncology
Miranda H Meeuwsen, Anne K Wouters, Tassilo L A Wachsmann, Renate S Hagedoorn, Michel G D Kester, Dennis F G Remst, Dirk M van der Steen, Arnoud H de Ru, Els P van Hees, Martijn Kremer, Marieke Griffioen, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
BACKGROUND: The immunoglobulin J chain (Jchain) is highly expressed in the majority of multiple myeloma (MM), and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM. METHODS: Using immunopeptidomics, we identified Jchain-derived epitopes presented by MM cells, and pHLA tetramer technology was used to isolate Jchain-specific T-cell clones. RESULTS: We identified T cells specific for Jchain peptides presented in HLA-A1, -A24, -A3, and -A11 that recognized and lysed JCHAIN-positive MM cells...
February 27, 2023: Journal of Hematology & Oncology
Jianshan Mo, Lin Deng, Keren Peng, Shumin Ouyang, Wen Ding, Linlin Lou, Ziyou Lin, Jianzheng Zhu, Jingwei Li, Qiyi Zhang, Pengyan Wang, Yuanzhen Wen, Xiaobing Chen, Peibin Yue, Jin-Jian Lu, Kai Zhu, Yongjiang Zheng, Yuanxiang Wang, Xiaolei Zhang
The acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML...
February 27, 2023: Journal of Hematology & Oncology
Dan Jin, Jiwei Guo, Yan Wu, Jing Du, Lijuan Yang, Xiaohong Wang, Weihua Di, Baoguang Hu, Jiajia An, Lingqun Kong, Lei Pan, Guoming Su
No abstract text is available yet for this article.
February 22, 2023: Journal of Hematology & Oncology
Qian Jiang, Zongru Li, Yazhen Qin, Weiming Li, Na Xu, Bingcheng Liu, Yanli Zhang, Li Meng, Huanling Zhu, Xin Du, Suning Chen, Yang Liang, Yu Hu, Xiaoli Liu, Yongping Song, Lichuang Men, Zi Chen, Qian Niu, Hengbang Wang, Ming Lu, Dajun Yang, Yifan Zhai, Xiaojun Huang
No abstract text is available yet for this article.
February 20, 2023: Journal of Hematology & Oncology
Qian Hua, Mingming Jin, Baoming Mi, Fei Xu, Tian Li, Li Zhao, Jianjun Liu, Gang Huang
No abstract text is available yet for this article.
February 18, 2023: Journal of Hematology & Oncology
Chiara Fallerini, Sergio Daga, Elisa Benetti, Nicola Picchiotti, Kristina Zguro, Francesca Catapano, Virginia Baroni, Simone Lanini, Alessandro Bucalossi, Giuseppe Marotta, Francesca Colombo, Margherita Baldassarri, Francesca Fava, Giada Beligni, Laura Di Sarno, Diana Alaverdian, Maria Palmieri, Susanna Croci, Andrea M Isidori, Simone Furini, Elisa Frullanti, Alessandra Renieri, Francesca Mari
No abstract text is available yet for this article.
February 15, 2023: Journal of Hematology & Oncology
Frédéric Baron, Myriam Labopin, Johanna Tischer, Anna Maria Raiola, Jan Vydra, Didier Blaise, Patrizia Chiusolo, Friedrich Stölzel, Renato Fanin, Patrice Chevallier, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
The association between graft-versus-host disease (GVHD) occurrence and acute myeloid leukemia (AML) relapse in patients treated with HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis has remained debated. Here, we addressed this issue in patients with active AML at transplantation. 2-year cumulative incidences of relapse and leukemia-free survival (LFS) were 49% and 32.3%, respectively. There were no associations between acute nor chronic GVHD of any grade and lower relapse incidence...
February 13, 2023: Journal of Hematology & Oncology
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